[Mechanism of Potentilla discolor in treating UC by regulating mitochondrial autophagy].

To evaluate the therapeutic effect of Potentilla discolor on 2,4,6-trinitrobenzensulfonic acid(TNBS)-induced experimental ulcerative colitis(UC) in rats and to determine its therapeutic mechanism through mitochondrial autophagy, immune cells, and cytokines. A rat model of UC was established by TNBS-ethanol enema. Rats were divided into six groups: control, UC model, sulfasalazine(positive drug), and high-dose, moderate-dose, and low-dose ethanol extract groups. After 14-day continuous administration of the corresponding drugs, the disease activity index(DAI) and hematoxylin and eosin(HE) were evaluated. The morphological structure of mitochondria was observed by using transmission electron microscope(TEM), mitophagy-related mRNA expression was detected by using Real-time quantitative polymerase chain reaction(qRT-PCR), immune cell differentiation in rat serum was detected by using flow cytometry(FCM), and cytokine expression in colon tissues of rats was detected by protein microarray. The results showed that compared with the model group, each dose group of P. discolor could significantly reduce the DAI of UC model rats, and decrease the degree of inflammatory cells infiltration in the colon tissue of UC model rats. Meanwhile the expressions of T cells and Th cells in the serum increased significantly, the expression of Tc cells in the serum decreased significantly. Transmission electron microscope found that there was fusion of mitochondria and lysosomes in the colon tissue of the administration group. The expressions of mitochondrial autophagy related genes NF-κB, p62 and parkin were significantly increased in colon tissues. The results of protein chip showed that compared with the model group, the high dose group of P. discolor could significantly regulate the expression of cytokines. In conclusion, these results suggested that P. discolor improved TNBS-induced acute ulcerative colitis in rats by regulating the mitochondrial autophagy and the inflammatory factor expression.

Comparative analysis of type 2 diabetes-associated gut microbiota between Han and Mongolian people.

Due to the different rates of diabetes in different ethnic groups and the structural differences in intestinal microbiota, this study evaluated the changes in diabetes-related intestinal microbiota in two ethnic groups. Fifty-six stool samples were collected from subjects from the Han and Mongolian ethnic groups in China, including participants without diabetes (non-diabetic, ND) and with type 2 diabetes (T2D). The 16S rDNA gene V3 + V4 area was extracted from microbiota, amplified by PCR, and used to perform high-throughput sequencing and screen differential microbiota associated with ethnicity. The results showed that there were 44 T2D-related bacterial markers in the Han subjects, of which Flavonifractor, Alistipes, Prevotella, Oscillibacter, Clostridium XlVa, and Lachnospiracea_incertae_sedis were most closely related to diabetes. There were 20 T2D-related bacterial markers in the Mongolian subjects, of which Fastidiosipila and Barnesiella were most closely related to diabetes. The common markers of T2D bacteria in the two ethnic groups were Papillibacter and Bifidobacterium. There were 17 metabolic pathways with significant differences between the ND and T2D groups in the Han group, and 29 metabolic pathways in the Mongolian group. The glutamatergic metabolic pathway was the only common metabolic pathway in two ethnic groups. The composition and function of diabetes-related bacteria were significantly different among the different ethnic groups, which suggested that the influence of ethnic differences should be fully considered when studying the association between diabetes and bacteria. In addition, the common bacterial markers found in diabetic patients of different ethnic groups in this study can be used as potential targets to study the pathogenesis and treatment of diabetes.

Hypoglycemic effects of Tibetan medicine Huidouba in STZ-induced diabetic mice and db/db mice.

Objective: Huidouba (HDB) is a Chinese folk medicine used to treat diabetes in Sichuan Province, China. Therefore, we investigated the anti-diabetic effects of HDB and its underlying mechanisms. We hypothesized that HDB treatment could enhance glucose tolerance and insulin sensitivity, and thus prevent a hyperglycemia state. Methods: To test the hypothesis, streptozotocin (STZ)-induced diabetic mice and db/db mice, widely used models of hyperglycemia and insulin-resistant diabetes, were either treated with HDB, metformin, or acarbose. Blood glucose, oral glucose tolerance test, insulin tolerance test, pancreatic histopathology and serum biochemistry were detected to assess the hypoglycemic effect of HDB. Results: HDB treatments were found to show the effect in reducing glucose levels. HDB also resulted in a significant reduction in body weight and food intake in the STZ-induced diabetic mouse model. Furthermore, it significantly improved glucose and insulin tolerance in the two diabetic mouse models. Importantly, insulin, glucagon, pancreatic polypeptide, and somatostatin immunohistochemistry revealed that HDB treatment improved the function and the location of the cells in the islets compared with the other two treatments. HDB treatment resulted in significant restoration of islet function. Our results illustrated the underlying mechanism of HDB in the progression of diabetes, and HDB can be an effective agent for the treatment of diabetes. Conclusion: The results of this study suggested that HDB can reduce blood glucose levels in STZ-induced hyperglycemic mice and db/db mice.

Regulatory effect of Garidisan on dysbiosis of the gut microbiota in the mouse model of ulcerative colitis induced by dextran sulfate sodium.

BACKGROUND: Ulcerative colitis (UC) is a modern refractory disease, and its etiology has been difficult to discern. Studies have shown that UC is closely associated with the gut microbiota. Garidisan is composed of wild poppy and Artemisia frigida Willd and is commonly used for the treatment of UC in Inner Mongolia, China. In clinical settings, Garidisan has been found to treat UC effectively, with low recurrence. Previous studies have shown that Garidisan has a good therapeutic effect on mice with UC, but the therapeutic mechanism is still unclear. In this study, we investigated the regulatory effect of Garidisan on dysbiosis of the gut microbiota in a UC mouse model and explored the possible mechanism of the therapeutic effect of Garidisan on UC. METHODS: The UC mouse model was established by the dextran sulfate sodium (DSS) circulating free water drinking method, and the luminal contents were sampled under sterile conditions. High-throughput sequencing of the 16S rRNA gene V3 + V4 region of the luminal contents of the control group, model group, and Garidisan group was conducted, and clustering of operational taxonomic units (OTUs) and species annotation were performed. The differences in species composition and microbial community structure between individual groups of samples were analyzed using MetaStat, LefSe, rank sum test, and Bayesian causal network analysis. RESULTS: The UC mouse model was successfully established and the sequencing results were of adequate quality. There were significant differences in the diversity of luminal contents between the control group, model group, and Garidisan group, and the differences between groups were greater than those within any group. The therapeutic effect of Garidisan on UC is attributed to the direct effect on the Lachnospiraceae family of bacteria. CONCLUSION: Garidisan has a good regulatory effect on the gut microbiota, and Lachnospiraceae could be an important direct target of Garidisan for the treatment of UC.

Role of colonic microbiota in the pathogenesis of ulcerative colitis.

BACKGROUND: Recent studies have found gut microbiota to be closely associated with onset and perpetuation of UC. Currently, studies about gut microbiota have mainly covered samples collected from the intestinal lumen. However, the luminal flora is only part of the gut microbiota. Studies of the changes in mucosal flora under pathological conditions have been lacking. In this study, we investigated the correlation between the onset of UC and flora changes in different intestinal layers. METHODS: The dextran sulfate sodium(DSS)-induced UC model was established by exposing mice to cycles of DSS. The luminal contents, an inner mucus layer, and outer mucus layer were harvested under sterile conditions. The samples were then analyzed using high-throughput sequencing of 16S rRNA V3 + V4 amplicons. The colonic microbiota composition and diversity were analyzed and compared using MetaStat, LefSe, multivariate analysis of variance, and spatial statistics. RESULTS: The DSS-induced UC mouse model was successfully established. The diversity of the microbiota from luminal content, the outer mucus layer, and inner mucus layer were significantly different in both control and UC model groups. The statistically different OTUs belonged to Lachnospiraceae and Ruminococcaceae families within the order Clostridiales were mainly localized to the outer mucus layer. CONCLUSIONS: The alterations in flora composition and diversity mainly occurred in the colonic outer mucus layer. The change of flora in the colonic mucus layers is of great significance in the understanding of common features of gut flora in IBD and the understanding of the relationship between gut flora and disease progression.

Application of BMD approach to identify thresholds of cadmium-induced renal effect among 35 to 55 year-old women in two cadmium polluted counties in China.

BACKGROUND: Cadmium (Cd) is a heavy metal that can cause renal tubular dysfunction in humans. Women are among the high-risk group for Cd health effects. Determining the thresholds of Cd-induced renal effects is important. Thus, in this article, we aimed to identify the benchmark dose (BMD) and its low limit (BMDL) levels as the Cd thresholds for Chinese women. METHODS: Epidemiologic investigation was performed in county A and county B to obtain data on Cd exposure and its renal effect on respondents. Levels of Cd (UCd), ß2-microglobulin (UB2M), and N-acetyl-ß-D-glucosaminidase (UNAG) were measured in morning urine samples. The BMD approach was mainly performed. RESULTS: Results of the BMD approach were similar whether the method was conducted for the two sets of data (collected in CA and CB, respectively) separately or cooperatively. The BMD/BMDL values of UCd for all subjects were 1.07/0.44 and 2.12/0.53 µg/g cr based on UB2M and UNAG, respectively, given a predetermined BMR of 0.05. CONCLUSIONS: The presented thresholds of Cd-induced renal effects (i.e., the BMDLs of UCd) are close to the counterpart values reported in Japan, Sweden and Belgium.

delta-Aminolevulinic acid dehydratase activity, urinary delta-aminolevulinic acid concentration and zinc protoporphyrin level among people with low level of lead exposure.

To evaluate the relationship of delta-aminolevulinic acid dehydratase (ALAD) activity, urinary delta-aminolevulinic acid (ALAU) level and blood zinc protoporphyrin (ZPP) concentration to low blood lead (PbB) levels, these biomarkers were determined for all subjects enrolled from a rural area of southeast China where people had low levels of exposure to lead. The mean values of PbB, ALAD, ALAU and ZPP were 67.11 microg/L (SD: 1.654, range: 10.90-514.04), 339.66 nmol ml(-1)h(-1) (1.419, 78.33-793.13), 20.64 microg/L (1.603, 2.00-326.00), and 0.14 micromol/L (3.437, 0.01-2.26), respectively. ALAD was inversely associated with low levels of PbB. ZPP was inversely related to low levels of PbB but positively related to relatively higher levels of PbB. Alcohol drinking contributed to low ALAD in men. Women had higher ZPP than men. ALAU had no significant association with PbB. In conclusion, ALAD possibly has a non-linear relation with low to moderate levels of PbB. At moderate levels of PbB, ZPP increases with increasing levels of PbB. ALAU is not suitable as an indicator for low levels of lead exposure.

[Assessment of the disability weight for chronic schistosomiasis japonica in lake region].

OBJECTIVE: To estimate a suitable disability weight for chronic schistosomiasis japonica in a lake area of China. METHODS: A total of 219 chronic schistosomiasis patients from surveillance sites in Yangxin County of Hubei Province received questionnairing. The age- and sex-specific disability weights of chronic schistosomiasis were estimated based on the six classes of disability severity identified by Global Burden of Disease (GBD). All data was managed by Epidata 3.1. Statistical analysis was performed using SAS8.1. Rank sum test and Kruskal-Wallis test were used to examine the differences between disability weights. Pair-wise comparison was done by Nemenyi method. Multifactor logistic regression was used to analyze the risk factors of disability weight. RESULTS: The average disability weight was 0.122, and age-specific weight ranged from 0.020 to 0.280. The disability weight increased with age. Significant differences were found among different age groups (chi2=152.590, P<0.01). The disability weight of males (0.103) was significantly lower (Z=2.405, P<0.05) than that of females (0.147). Multi-factor logistic regression models indicated that the disability weight was significantly associated with age (OR=1.173, 95% CI: 1.130-1.217), and income level was a protective factor (OR=0.497, 95% CI: 0.319-0.775), while age was a confounding factor. CONCLUSION: An average disability weight of 0.122 for chronic schistosomiasis japonica indicates that 1/8 healthy year has lost for each survived life year of the patients, higher than the data of GBD.

[Study on the reliability, validity and sensitivity of a Family Burden Scale used for evaluation on schistosomiasis].

OBJECTIVE: To evaluate the reliability, validity and sensitivity of a Family Burden Scale (FBS) of disease used on schistosomiasis. METHODS: 224 schistosomiasis patients were investigated, using the FBS. Reliability was estimated by Cronbach's alpha coefficient and split-half reliability. Validity was tested by factor analysis. Sensitivity was evaluated by comparison of patients with different income levels. RESULTS: The Cronbach's alpha coefficient was 0.874 and split-half reliability was 0.939 for FBS, respectively. Most values of Cronbach's alpha and split-half reliability for each component of scale were above 0.70. Construct validity was appraised by factor analysis, and 6 factors were identified. These factors could explain 66.76% of the total variance. Patients with different income levels showed significant difference in terms of family burden for schistosomiasis (P < 0.001). CONCLUSION: This FBS appeared to have satisfactory reliability, validity and sensitivity and could be used in evaluating family burden of schistosomiasis patients.

[Logistic analysis on risk factors related to smear positive pulmonary tuberculosis].

OBJECTIVE: To explore the risk factors on relapsing tuberculosis related to smear positive pulmonary tuberculosis which had been cured for five years. METHODS: Patients with smear positive pulmonary tuberculosis registered in 1995 from ten countries in Hubei province were studied and logistic regression was used for data analysis. RESULTS: The 5-year relapse rate of smear positive pulmonary tuberculosis was 3.85 percent. Risk factors related to relapse would include being non-modeled county, negative smear after treated for three months, the class of retreatment, management of non-DOTS, method of chemotherapy and patients that did not get treated by the tuberculosis institute, with odds ratios of 0.15, 4.62, 3.68, 5.88 and 6.47, respectively. CONCLUSION: Effect standard, regulation DOTS and the centralized management measure might have had effects on decreasing the relapse rate.